Molecular dynamics of amphotericin B I. Single molecule in vacuum and water

Molecular dynamics simulations were performed for an antifungal polyene antibiotic amphotericin B (AMB). A single molecule of the AMB was modeled in vacuum as well as in water. In the latter case it was surrounded by 354 SPC water molecules and a periodic boundary condition was applied. An amino-sugar mycosamine ring was found to be rigid in the conditions studied. The mean orientation of this ring in relation to a macrolide ring was found to be common in both simulations and similar to that observed in a crystal of N-iodoacetyl derivative. A large flexibility of the amino-sugar orientation was observed in vacuum in contrast to water simulation. Several conformers of the macrolide ring were observed in vacuum as well as in water simulation. Interactions which may force these conformational transitions have been proposed. The structuring of the water molecules around polar and ionizable parts of the AMB molecule were analysed. The influence of the dynamic behavior of the AMB on structures of supramolecular complexes containing this antibiotic is discussed.